About the safety issue of long-term weightlessness astronauts suffer from - have they considered using a paraplegic (seriously) for long space missions? If the guy can’t walk anyway, what difference would it make when he came back? His mind and arms would still serve satisfactorily without the ill effects.
I don’t know the full answer to your question, but even though you can’t walk in microgravity, I imagine that the astronauts still use their legs, just for mobility.
Legs are constantly bumping into things in microgravity. They also represent a non-trivial amount of mass.
An optimal solution would be to crew any long-term space missions with amputees.
You still need to brace yourself for leverage even in weightless conditions. Legs are a necessity.
Besides which, the effects of microgravity aren’t limited to the legs. Arms, torsos and necks also atrophy and lose bone mass while in space. A paraplegic would lose ability in the parts he can still use, too, so he would have no advantage on return to Earth.